Prism adaptation is a well-known method used to investigate brain plasticity, and a promising technique for the rehabilitation of unilateral spatial neglect (USN). Only little evidence about the mechanisms of prism adaptation (PA) in patients with left-brain damage is on record, and about putative differences of PA, and the aftereffects (AEs), between patients with left and right brain damage. In the present study, PA and the AEs were assessed in 30 brain-damaged patients, 20 with right-sided lesions (10 with and 10 without USN), and 10 with left-sided lesions without USN, as well as in a control group of 24 age-matched participants. All patients underwent adaptation to lenses shifting the field of vision towards the side of the lesion, followed by two measures for detecting AEs: the proprioceptive (P) and the visuo-proprioceptive (VP) straight-ahead tasks. To investigate the temporal course of AEs in the different groups, the two measures were recorded immediately and 10 min after PA. Before PA, and at the end of the 10-min delayed evaluation, two tasks to assess USN (target cancellation and drawing) were also administered. All patients adapted to prisms. However, left-brain-damaged (LBD) patients presented with reduced AEs, as compared with right-brain-damaged (RBD) patients with USN. Moreover, while both controls and LBD patients adapting to left-shifting prisms had reduced VP AEs in the delayed condition, AEs were not different from zero (i.e., no AEs) in LBD patients. Finally, in the delayed condition USN patients showed an improvement in the drawing, but not in the cancellation, tasks. These results suggest that adaptation to leftward shifting lenses is associated with larger decay of VP AEs, and a role of the left hemisphere in maintaining these AEs after PA. These findings can be of relevance for the clinical application of this technique in neurological populations.

The disownership of body parts, that most frequently occurs on the left side of the body, contralateral to right-hemispheric lesions, is an infrequent disorder, as usually assessed by interviews asking for dichotomic "yes/no" responses. This observational study in right-brain-damaged stroke patients investigated the efficacy of a continuous Visual Analog Scale (VAS) to detect body disownership after right brain damage, compared to dichotomic questions. Thirty-two right-handed right-brain-damaged stroke patients were given a Standardized Interview (SI), asking "Whose hand/arm/leg is this?", followed by a VAS (asking patients to mark on a vertical line their agreement with the statement that a body part belonged to them). The neural correlates of this disorder and measures of extra-personal and personal spatial neglect were also assessed. Control data were recorded from 18 neurologically unimpaired right-handed participants. During the interview, no patient showed disownership of body parts. Conversely, on the VAS eight out of 32 (25%) patients' scores, but none of the controls' scores, indicated a judgement of disownership for left body parts, with a left-right difference larger than that of control participants. VAS-detected disownership was not systematically associated with extra-personal and personal unilateral spatial neglect. Lesion sites associated with disownership of left body parts included the caudate nucleus and the anterior part of the internal capsule. To conclude, the VAS task, compared to the interview, is a novel tool to detect disownership of left body parts in right brain-damaged patients. A revised classification of body-ownership disorders is proposed. The present variant, assessed and detected by the VAS task, is termed Covert disownership and distinguished from the Overt disownership assessed by a SI.

Transcranial direct current stimulation (tDCS) is increasingly used in both research and therapeutic settings, but its precise mechanisms remain largely unknown. At a neuronal level, tDCS modulates cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate, while cathodal decreases it. However, the neurophysiological underpinnings of anodal/cathodal tDCS seem to be different, as well as their behavioral effect, in particular when high order areas are involved, compared to when motor or sensory brain areas are targeted. Previously, we investigated the effect of anodal tDCS on cortical excitability, by means of a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results showed a diffuse rise of cortical excitability in a bilateral fronto-parietal network. In the present study, we tested, with the same paradigm, the effect of cathodal tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 10 min of cathodal or sham tDCS over the right PPC, while recording HD-EEG. Indexes of global and local cortical excitability were obtained both at sensors and cortical sources level. At sensors, global and local mean field power (GMFP and LMFP) were computed for three temporal windows (0-50, 50-100, and 100-150 ms), on all channels (GMFP), and in four different clusters of electrodes (LMFP, left and right, in frontal and parietal regions). After source reconstruction, Significant Current Density was computed at the global level, and for four Broadmann's areas (left/right BA 6 and 7). Both sensors and cortical sources results converge in showing no differences during and after cathodal tDCS compared to pre-stimulation sessions, both at global and local level. The same holds for sham tDCS. These data highlight an asymmetric impact of anodal and cathodal stimulation on cortical excitability, with a diffuse effect of anodal and no effect of cathodal tDCS over the parietal cortex. These results are consistent with the current literature: while anodal-excitatory and cathodal-inhibitory effects are well-established in the sensory and motor domains, both at physiological and behavioral levels, results for cathodal stimulation are more controversial for modulation of exitability of higher order areas.

The Rivermead assessment of somatosensory performance (RASP) provides a quantitative assessment of somatosensory processing, suitable for brain-damaged patients suffering from stroke. It consists of seven subcomponents: Subtest 1 (sharp/dull discrimination), Subtest 2 (surface pressure touch), Subtest 3 (surface localization), Subtest 4 (sensory extinction), Subtest 5 (2-point discrimination), Subtest 6 (temperature discrimination), and Subtest 7 (proprioception). Overall, the RASP assesses 5 bilateral body regions: face (cheek), hand (palm and back), and foot (sole and back). This study aimed at providing normative data and cut-off scores for RASP subtests, for each body region, in a large Italian population sample. We present results from 300 healthy Italian individuals aged 19 to 98 years. Data represent a comprehensive set of norms that cover each subtest and each body region tested. Performance in Subtests 1, 5, and 6 decreased, for some body regions, with increasing age. Based on these results, norms were stratified for age (seven groups), with the pathological/non-pathological cut-off coinciding with the 5th percentile. Conversely, other results were not influenced by age; in such cases, a single error, in each body region, has to be considered indicative of pathological performance. This independent investigation of all subcomponents of the somatosensory system, for each body region, further confirms RASP's potential in clinical practice, for neurological assessment, as well as in research settings.

Unilateral spatial neglect (USN) has been mainly investigated in the visual modality; only few studies compared spatial neglect across different sensory modalities, and explored their multisensory interactions, with controversial results. We investigated the integration between vision and haptics, through a bisection task of a cross modal illusion, the Judd variant of the Müller-Lyer illusion. We examined right-brain-damaged patients with (n = 7) and without (n = 7) left USN, and neurologically unimpaired participants (n = 14) in the bisection of Judd stimuli under visual, haptic, and visuo-haptic presentation. Neglect patients showed the characteristic rightward bias in the bisection of the baseline stimuli in the visual modality, but not in the haptic and visuo-haptic conditions. The illusory effects were preserved in each group and in each modality, indicating that the processing of the cross modal illusion is independent of the presence of deficits of spatial attention and representation. Spatial neglect can be modality-specific, but visual and tactile sensory inputs are properly integrated.

Transcranial direct current stimulation (tDCS) is a non-invasive tool, which effectively modulates behavior, and related brain activity. When applied to the primary motor cortex (M1), tDCS affects motor function, enhancing or decreasing performance of both healthy participants and brain-damaged patients. Beyond M1, the posterior parietal cortex (PPC) is also crucially involved in controlling and guiding movement. Therefore, we explored whether the modulation of cortical excitability within PPC can also affect hand motor function in healthy right-handed participants. In Experiment 1, anodal tDCS (2 mA, 10 min) was applied to PPC and to M1 of both hemispheres. Skilled motor function of the non-dominant left hand, measured using the Jebsen-Taylor Hand Function Test (JTT), improved after anodal tDCS of the right, contralateral M1, as well as after the anodal stimulation of the left, ipsilateral PPC. Conversely, in Experiment 2, cathodal tDCS of the left PPC, or of the right M1, reduced motor performance of the left hand. Finally, Experiment 3 shows that the anodal tDCS of the left PPC selectively facilitated action planning, while the anodal tDCS of the right M1 modulated action execution only. This evidence shows that motor improvement induced by left parietal and right motor stimulations relies on substantial different mechanisms, opening up novel perspectives in the neurorehabilitation of stroke patients with motor and apraxic disorders.

In line bisection right-brain-damaged patients with left spatial neglect show a rightward deviation, with respect to the line's physical center. In word bisection ortho-phonological features of the stimulus' final (right-sided) part modulate performance of both patients and healthy participants (Veronelli, Vallar, Marinelli, Primativo, & Arduino, 2014). We investigated the role of linguistic factors in sentence bisection, in patients with and without neglect, and control participants. The effects of information in the right-sided part of the sentence (Experiment #1), and of lexical and syntactic violations (Experiment #2) were assessed. Neglect patients showed an overall rightward bias, larger than those of patients without neglect and controls. The neglect patients' bias was modulated by stimulus type, decreasing from lines, to letter strings and to all types of sentences. In sum, in visuo-manual sentence bisection a basic linguistic mechanism, such as sentence readability, brings about a more leftward appreciation of the stimulus, reducing the neglect patients' rightward bias.

There is evidence that humans represent numbers in the form of a mental number line (MNL). Here we show that the MNL modulates the representation of visual and haptic space both in healthy individuals and right-brain-damaged patients, both with and without left unilateral spatial neglect (USN). Participants were asked to estimate the midpoint of visually or haptically explored rods while listening to task-irrelevant stimuli: a small digit ("2"), a large digit ("8"), or a non-numerical auditory stimulus ("blah"). In a control silent condition, the bisection error of USN patients was biased rightwards (namely, the marker of USN) only in the visual modality. Regardless of the direction of the bisection error committed in silent trials, listening to the small digit shifted the perceived midline leftwards, and listening to the large digit shifted the perceived midline rightwards, compared to a control condition in which a neutral syllable ("blah") was presented. The shift induced by listening to numbers occurred independently of the modality of response (i.e., both in vision and haptics), and in every group of participants. Interestingly, the effect of auditory numbers processing on space estimation was overall larger for haptically than for visually explored space in all participants. In conclusion, the present data show that listening to irrelevant numbers affects space perception also in patients with left USN, indicating that the spatial representation and attention processes disrupted by USN are not involved in these numerical magnitude-spatial effects.

Converging evidence on voluntary actions underlays the existence of a motor monitoring system able to compare the predicted and the actual consequences of our movements. In this context, both the premotor cortex (PMC) and the posterior parietal cortex (PPC) play a role in action monitoring and awareness. The present study explores the role of PMC and PPC in monitoring involuntary muscle contractions induced by transcranial magnetic stimulation (TMS) over the hand motor area. To this aim, the effects of transcranial direct current stimulation (tDCS) over PMC and PPC were examined. Thirty-six healthy subjects were asked to perform a motor monitoring task (i.e., to verbally report hand twitches induced by TMS) after 10 min of tDCS. Through three experiments, the effects of cathodal, anodal and sham tDCS over the left and the right hemispheres were compared. Our results show that cathodal tDCS over the right PMC does not affect the monitoring of involuntary movements. By contrast, tDCS over both the right and the left PPC affects motor monitoring, depending on the current polarity: while cathodal tDCS increases the feeling of phantom-like movements (which actually did not occur), anodal tDCS impairs the ability to detect involuntary hand twitches (which actually took place). These findings show that the PMC is not involved in motor monitoring of involuntary movements; rather, the PPC, where multisensory stimuli converge and are processed, seems to play a crucial role.

Since the 1960s, evidence from healthy participants and brain-damaged patients, neuroimaging and non-invasive brain stimulation studies has specified the neurofunctional architecture of the short-term memory (STM) system, supporting the temporary retention of a limited amount of verbal material. Auditory-verbal, later termed Phonological (Ph) STM or Phonological Loop, comprises two sub-components: i) the main storage system, the Phonological Short-Term Store (PhSTS), to which auditory verbal stimuli have direct access and where phonologically coded information is retained for a few seconds; ii) a Rehearsal Process (REH), which actively maintains the trace held in the PhSTS, preventing its decay and conveys visual verbal material to the PhSTS, after the process of Phonological Recoding (PhREC, or Grapheme-to-Phoneme Conversion) has taken place. PhREC converts visuo-verbal graphemic representations into phonological ones. The neural correlates of PhSTM include two discrete regions in the left hemisphere: the temporo-parietal junction (PhSTS) and the inferior frontal gyrus in the premotor cortex (REH). The neural basis of PhREC has been much less investigated. A few single case studies of patients made anarthric by focal or degenerative cortical damage, who show a pattern of impairment indicative of a deficit of PhREC, sparing the REH process, suggest that the primary motor cortex (M1) might be involved. To test this hypothesis in healthy participants with a neurophysiological approach, we measured the corticospinal excitability of M1, by means of Transcranial Magnetic Stimulation (TMS)-induced Motor Evoked Potentials (MEPs), during the execution of phonological judgements on auditorily vs. visually presented words (Experiment #1). Crucially, these phonological tasks involve REH, while PhREC is required only with visual presentation. Results show MEPs with larger amplitude when stimuli are presented visually. Task difficulty does not account for this difference and the result is specific for linguistic stimuli, indeed visual and auditory stimuli that cannot be verbalized lead to different behavioral and neurophysiological patterns (Experiment #2). The increase of corticospinal excitability when words are presented visually can be then interpreted as an indication of the involvement of M1 in PhREC. The present findings elucidate the neural correlates of PhREC, suggesting an involvement of the peripheral motor system in its activity.

Humans are the only species capable of experiencing pleasure from esthetic stimuli, such as art and music. Neuroimaging evidence suggests that the left dorsolateral prefrontal cortex (DLPFC) plays a critical role in esthetic judgments, both in music and in visual art. In the last decade, non-invasive brain stimulation (NIBS) has been increasingly employed to shed light on the causal role of different brain regions contributing to esthetic appreciation. In Experiment #1, musician (N = 20) and non-musician (N = 20) participants were required to judge musical stimuli in terms of "liking" and "emotions". No significant differences between groups were found, although musicians were slower than non-musicians in both tasks, likely indicating a more analytic judgment, due to musical expertise. Experiment #2 investigated the putative causal role of the left dorsolateral pre-frontal cortex (DLPFC) in the esthetic appreciation of music, by means of transcranial direct current stimulation (tDCS). Unlike previous findings in visual art, no significant effects of tDCS were found, suggesting that stimulating the left DLPFC is not enough to affect the esthetic appreciation of music, although this conclusion is based on negative evidence,.

In recent years we reported three right-brain-damaged patients, who exhibited a left-sided disprortionate expansion of drawings, both by copying and from memory, contralateral to the side of the hemispheric lesion (Neurology, 67: 1801, 2006, Neurocase 14: 369, 2008). We proposed the term "hyperschematia" for such an expansion, with reference to an interpretation in terms of a lateral leftward distortion of the representation of extra-personal space, with a leftward anisometric expansion (relaxation) of the spatial medium. The symptom-complex shown by right-brain-damaged patients with "hyperschematia" includes: (1) a disproportionate leftward expansion of drawings (with possible addition of details), by copy and from memory (also in clay modeling, in one patient); (2) an overestimation of left lateral extent, when a leftward movement is required, associated in some patients with a perceptual underestimation; (3) unawareness of the disorder; (4) no unilateral spatial neglect. In most right-brain-damaged patients, left "hyperschematia" involves extra-personal space. In one patient the deficit was confined to a body part (left half-face: personal "hyperschematia"). The neural underpinnings of the disorder include damage to the fronto-temporo-parietal cortices, and subcortical structures in the right cerebral hemisphere, in the vascular territory of the middle cerebral artery. Here, four novel additional patients are reported. Finally, "hypeschematia" is reconsidered, in its clinical components, the underlying pathological mechanisms, as well as its neural underpinnings.

Despite transcranial direct current stimulation (tDCS) is increasingly used in experimental and clinical settings, its precise mechanisms of action remain largely unknown. At a neuronal level, tDCS modulates the resting membrane potential in a polarity-dependent fashion: anodal stimulation increases cortical excitability in the stimulated region, while cathodal decreases it. So far, the neurophysiological underpinnings of the immediate and delayed effects of tDCS, and to what extent the stimulation of a given cerebral region may affect the activity of anatomically connected regions, remain unclear. In the present study, we used a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG) in order to explore local and global cortical excitability modulation during and after active and sham tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 15 min of tDCS over the right PPC, while EEG was recorded from 60 channels. For each session, indexes of global and local cerebral excitability were obtained, computed as global and local mean field power (Global Mean Field Power, GMFP and Local Mean Field Power, LMFP) on mean TMS-evoked potentials (TEPs) for three temporal windows: 0-50, 50-100, and 100-150 msec. The global index was computed on all 60 channels. The local indexes were computed in six clusters of electrodes: left and right in frontal, parietal and temporal regions. GMFP increased, compared to baseline, both during and after active tDCS in the 0-100 msec temporal window. LMFP increased after the end of stimulation in parietal and frontal clusters bilaterally, while no difference was found in the temporal clusters. In sum, a diffuse rise of cortical excitability occurred, both during and after active tDCS. This evidence highlights the spreading of the effects of anodal tDCS over remote cortical regions of stimulated and contralateral hemispheres.

Visuo-motor adaptation to optical prisms (Prism Adaptation, PA), displacing the visual scene laterally, is a behavioral method used for the experimental investigation of visuomotor plasticity, and, in clinical settings, for temporarily ameliorating and rehabilitating unilateral spatial neglect. This study investigated the building up of PA, and the presence of the typically occurring subsequent Aftereffects (AEs) in a brain-damaged patient (TMA), suffering from apperceptive agnosia and a right visual half-field defect, with bilateral atrophy of the parieto-occipital cortices, regions involved in PA and AEs. Base-Right prisms and control neutral lenses were used. PA was achieved by repeated pointing movements toward three types of stimuli: visual, auditory, and bimodal audio-visual. The presence and the magnitude of AEs were assessed by proprioceptive, visual, visuo-proprioceptive, and auditory-proprioceptive straight-ahead pointing tasks. The patient's brain connectivity was investigated by Diffusion Tensor Imaging (DTI). Unlike control participants, TMA did not show any adaptation to prism exposure, but her AEs were largely preserved. These findings indicate that AEs may occur even in the absence of PA, as indexed by the reduction of the pointing error, showing a dissociation between the classical measures of PA and AEs. In the PA process, error reduction, and its feedback, may be less central to the building up of AEs, than the sensorimotor pointing activity per se.

Spatial neglect is a debilitating disorder frequently observed after damage to the right cerebral hemisphere. Previous investigations have revealed that prism adaptation (PA) therapy can lead to improvements in neglect-related symptoms. In the typical PA protocol patients repeatedly point toward a visual target while wearing prism goggles. A few years ago, a novel PA procedure, involving a variety of more "ecological" visuo-motor activities during adaptation, less repetitive than a sequence of pointings, was introduced by our research group, and shown to be able to improve neglect-related symptoms to the same extent as the standard pointing task. The ecological procedure was easy to administer and pleasant for the patients. In all previous studies, patients were treated by specialized personnel during hospitalization. In the current study, we investigated the effectiveness of the ecological PA method when performed in a home-based setting, with the help of caregivers and family members. Seven right-brain-damaged patients with chronic left spatial neglect underwent a two-week ecological PA treatment, extended, for two extra weeks, in 6 patients, who were available for this additional rehabilitation session. As a control treatment, patients performed the same activities while wearing neutral goggles, before the PA procedure. Two weeks of ecological PA training proved to be able to significantly improve performance in neuropsychological tests (BIT, Cancellation tasks), a neurological scale (NIH), and functional abilities (CBS), when compared to both the baseline and the neutral control treatment, with improvements being maintained over 6 months. The ecological home-based PA training is effective in alleviating signs of spatial neglect. Importantly, this training is affordable, pleasant, and feasible to be performed in the comfort of the patient's home. Easily extendable to larger patient populations and prolonged periods, this method has a real potential to benefit the quality of life of brain-damaged patients with left spatial neglect.

The human brain has a remarkable capacity to focus processing resources based on the features and the relevance of the task at hand. The two cerebral hemispheres contribute differentially to this capacity, with the left hemisphere linguistic and right hemisphere visuo-spatial abilities each offering unique contributions. For example, previous research has established that healthy participants set the subjective mid-point of written sentences more leftwards of center, compared to unpronounceable letter strings or simple lines. Remarkably, patients with right hemisphere damage exhibiting unilateral spatial neglect also show this pattern, even though, as well known in the literature, they tend toward a rightward- bias for non-linguistic stimuli. This evidence suggests that the leftward bias for sentential material is due to linguistic, mainly left-hemisphere mediated processes, which are largely unimpaired in right brain-damaged patients, and intact in heathy participants. To test this hypothesis, we compared sentence bisection performance to that of letter strings and simple lines in left brain-damaged patients (with and without aphasia). If the larger leftward bias in the bisection of sentential material is based on linguistic processes, then the left brain-damaged patients should show a reduction or absence of a leftward bias in sentence bisection. We tested twenty-four left brain-damaged patients (12 with aphasia and 12 without aphasia), and 24 age-matched elderly participants (patients and controls were all right-handed). Participants were asked to bisect 240 stimuli, comprising: (i) affirmative and interrogative clauses, (ii) sentences with lexical and syntactic violations, (iii) letter strings and (iv) simple lines. As predicted, neurologically intact participants showed larger leftward biases in bisecting written readable sentences compared to strings of letters. In contrast, the left hemispheredamaged patients (both with and without aphasia) showed no differences in bisecting sentences and letter strings or lines. These findings indicate that the larger leftward bias exhibited by healthy participants in the bisection of sentences is likely due to ortho-phonological coding taking place implicitly during the bisection task. This ortho-phonological coding is impaired with left brain damage - also in absence of apparent aphasia - leading to the left hemispheredamaged patients showing a reduced leftward bias in sentence bisection. These findings support the hypothesis that the leftward bias in the bisection of written sentences is the result of ortho-phonological influences rather than visual-spatial biases.